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What Is Activated Protein C?

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  • Written By: S. Berger
  • Edited By: Shereen Skola
  • Last Modified Date: 05 November 2016
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    Conjecture Corporation
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Activated protein C (APC) is a protein that is involved in processes like inflammation and the clotting of blood. It circulates through the blood in its inactive form, and is only rendered active when bound to another protein called thrombin. When it is activated, it degrades proteins like Factor V and Factor VIIIa. These proteins normally increase thrombin levels, so protein C serves as a negative feedback mechanism. In essence, it prevents blood clot overactivity.

Severe immune responses to infections can lead to a life-threatening condition called sepsis. Activated protein C has been used successfully as a severe sepsis treatment. It can reduce the inflammation response from white blood cells like leukocytes, as well as from endothelial cells. In the presence of this protein, cells will release lower levels of certain interleukins and tumor necrosis factor-alpha. These compounds encourage inflammation and septic shock, and decreasing their output helps to protect nearby cells.

Another important way that activated protein C protects tissue is through its effects on blood vessels. Endothelial cells that line the blood vessels normally become permeable during an immune response to allow immune cells to enter tissue. In the presence of APC, they remain impermeable, keeping immune cells from targeting tissue for destruction. Due to these protective effects, this protein has become an approved septic shock treatment.

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Studies using mice have discovered how activated protein C improves survival rates after sepsis. Both endothelial cells and leukocytes have receptors for this protein on their surface. When this protein binds to the receptors, a cell signaling system is activated. Affected endothelial cells work to stabilize blood pressure and prevent leakage of fluid from tissue. Leukocytes release fewer pro-inflammatory compounds, and show a decreased response to these compounds after binding to APC.

Deficient forms of the gene coding for activated protein C can contribute to disease states. One mutation can make cells unable to produce APC. Possessing a single copy of this gene can lead to the formation of blood clots in veins, known as venous thrombosis. Two deficient copies leads to widespread clotting, and is usually fatal.

Other medical conditions involve a resistance to APC, where the protein is made improperly. Usually, this mutation results in activated protein C becoming unable to cleave and inactivate Factor V and Factor VIIIa. The symptoms of this resistance are indistinguishable from a partial or total lack of APC. As a result, individuals with this mutation are much more likely to develop thrombosis.

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